C1orf163/RESA1 is a novel mitochondrial intermembrane space protein connected to respiratory chain assembly

J Mol Biol. 2014 Feb 20;426(4):908-20. doi: 10.1016/j.jmb.2013.12.001. Epub 2013 Dec 9.

Abstract

Oxidative phosphorylation (OXPHOS) in mitochondria takes place at the inner membrane, which folds into numerous cristae. The stability of cristae depends, among other things, on the mitochondrial intermembrane space bridging complex. Its components include inner mitochondrial membrane protein mitofilin and outer membrane protein Sam50. We identified a conserved, uncharacterized protein, C1orf163 [SEL1 repeat containing 1 protein (SELRC1)], as one of the proteins significantly reduced after the knockdown of Sam50 and mitofilin. We show that C1orf163 is a mitochondrial soluble intermembrane space protein. Sam50 depletion affects moderately the import and assembly of C1orf163 into two protein complexes of approximately 60kDa and 150kDa. We observe that the knockdown of C1orf163 leads to reduction of levels of proteins belonging to the OXPHOS complexes. The activity of complexes I and IV is reduced in C1orf163-depleted cells, and we observe the strongest defects in the assembly of complex IV. Therefore, we propose C1orf163 to be a novel factor important for the assembly of respiratory chain complexes in human mitochondria and suggest to name it RESA1 (for RESpiratory chain Assembly 1).

Keywords: CPOX; IMM; IMS; MIB; MINOS; OMM; OXPHOS; SEL1 repeat containing 1 protein; SEL1-like repeat; SELRC1; SILAC; SLR; Sam50; TOM; coproporphyrinogen oxidase; cristae; inner mitochondrial membrane; intermembrane space; mitochondria; mitochondrial inner membrane organizing system; mitochondrial intermembrane space bridging; outer mitochondrial membrane; oxidative phosphorylation; shRNA; short hairpin RNA; stable isotope labeling with amino acids in cell culture; translocase of the outer membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Electron Transport Complex IV / metabolism
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Sequence Data
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Oxidative Phosphorylation
  • Protein Transport
  • Solubility

Substances

  • COA7 protein, human
  • IMMT protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Muscle Proteins
  • SAMM50 protein, human
  • Electron Transport Complex IV